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Abstract

An efficient and economical low-pressure liquid chromatography process has been developed for paclitaxel recovery and purification directly from plant-tissue culture (PTC) broth. PTC broth is first diluted with ethanol to ensure padlitaxel dissolution and then passed through a column packed with a high-capacity polystyrene divinyl-benzene sorbent. A step increase in ethanol concentration in the mobile phase (ethanol:water) is used to concentrate and compress the taxane bands to as high as 29-fold of influent concentrations (about 1 mg/L). A recycle technique is then used to separate the concentrated paclitaxel band from other taxane bands, achieving 95% purity with more than 90% recovery and 99% purity with more than 80% recovery. In this process, the same low-pressure columns are used to capture, concentrate and purify paclitaxel. Theoretical predictions agree closely with the stepwise elution and recycle chromatography data. After validation, simulations are used to explore various design and operating alternatives. Analysis of the alternatives shows that the process cost can be further reduced by using higher feed concentration, larger loading volume, smaller particle size, and optimal gradient and recycle strategies.